By: April Carson
Synthetic biology has had remarkable success engineering yeast and bacteria to create chemicals—biofuels, pharmaceuticals, scents, even the hoppy tastes of beer—cheaply and sustainably with only sugar as a power source.
Yet the limitation of the field is that microbes, even with genes added from plants or other animals, can only construct compounds via natural chemical reactions. The bulk of chemistry and the chemical industry is concerned with producing things that do not exist in nature through laboratory-invented reactions.
Until recently, this has been a major problem for synthetic chemists and synthetic biologists, with research institutions such as the University of California at Berkeley's Synthetic Chemistry Lab and Lawrence Berkeley National Laboratory.
The researchers said that while the biochemistry in E. coli produced a low-value product in limited amounts, the fact that they were able to engineer a microbe to create something new in nature opens the door for bacterial fermentation and yeast production of a wider range of chemicals.
It's a brand-new method of chemical synthesis. The concept of developing an organism that creates such an unnatural product, which mixes laboratory synthesis with synthetic biology within a living being—it's just a futuristic approach to produce organic chemicals from two separate disciplines of science in a manner no one has done before," said John Hartwig, UC Berkeley chemistry professor and co–principal investigator of the study.
Synthetic biologists could use the techniques developed by this study to develop medicines that are more effective, less damaging, and less expensive than existing ones. The research may help advance synthetic biology's applications in a number of ways, including making medicines that are better, more sustainable alternatives to current drugs.
"What a lot of people don't understand is that they're going to need those materials eventually. This technology has the potential to create fuels with excellent qualities that can be produced sustainably, as well as new antibiotics, new nutraceuticals, and other compounds that would be extremely difficult to make using only biology or chemistry," she added. "
Metal catalysis is being hybridized with natural enzymes
Dr. Nicholas Ham, a senior staff scientist at Lawrence Berkeley National Laboratory and the Henry Rapoport Professor in Organic Chemistry at UC Berkeley, has developed artificial metalloenzymes that can manufacture compounds that have been difficult to produce in the laboratory using natural enzymes as metal catalysts.
Another area in which he and his lab have experimented with for the last six years is combining a cyclopropane—a ring made up of three carbon atoms—into other molecules. Such cyclopropanated compounds are becoming increasingly useful in medicine, such as a medication to cure hepatitis C infections.
A metalloenzyme they created is a hybrid of a natural enzyme, P450—widely used in the body, particularly in the liver, to oxidize compounds—and metal iridium. P450 naturally incorporates a cofactor called heme—also at the center of the hemoglobin molecule that transports oxygen in blood—that contains iron.
The metalloenzymes produced by Hartwig's lab also include a third carbon atom to modify other organic molecules in test tubes. The iridium-based metalloenzyme accomplishes this stereospecificity, which means it creates a cyclopropanated molecule but not its mirror image, which would have distinct biological effects.
To assess the potential of this approach, Dr. Gee's team collaborated with Professor Keasling's team at UC Berkeley to see if they could implement the iridium-containing heme into P450 enzymes inside living E.coli cells and give the bacteria the ability to produce cyclopropanated molecules entirely within the cell.
They discovered a method to transport the heme molecule with the iridium into E. coli, where most of the iridium added to the medium in which the bacteria grow was absorbed by a P450 enzyme.
The researchers then adjusted the bacteria's metabolism in order to make the final product, a cyclopropanated limonene, in a living bacterial culture.
"The product is a simple molecule, but the research demonstrates the capacity to link biochemis-tries and chemical synthesis in order to produce molecules that have never been made by organisms before, and nature has never produced," Hartwig said.
"These enzymes are tremendous due to the fact that they can be used with different metals. They're also capable of producing sustainable fuels and drugs, as well as biochemicals like collagen," said Mukhopadhyay about metalloenzymes.
"Today, many drugs are laboriously extracted from plants that are difficult to grow and pollute the environment. Making these chemicals in a lab using biotechnology would really address a lot of these issues," she continued.
"We're not just talking about medicines," she continued. "We're also talking about the precursors to polymers, renewable plastics, biofuels, building materials, and the full gamut of products we use today from detergents to lubricants to paints to pigments to textiles. Everything can be manufactured via biological processes.
"The larger goal is to be able to create synthetic organisms that generate non-natural chemicals by combining natural chemistry with laboratory chemistry," Hartwig added. "However, the chemical reactions would now take place inside a cell. If we could do this in a broad sense, we could engineer organisms to produce all sorts of medicines, agrochemicals, and novel materials."
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About the Blogger:
April Carson is the daughter of Billy Carson. She received her bachelor's degree in Social Sciences from Jacksonville University, where she was also on the Women's Basketball team. She now has a successful clothing company that specializes in organic baby clothes and other items. Take a look at their most popular fall fashions on bossbabymav.com
To read more of April's blogs, check out her website! She publishes new blogs on a daily basis, including the most helpful mommy advice and baby care tips! Follow on IG @bossbabymav
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